Prenatal Alcohol Exposure Affects Frontal–Striatal BOLD Response During Inhibitory Control Susanna L. Fryer, Susan F. Tapert, Sarah N. Mattson, Martin P. Paulus, Andrea D. Spadoni, and Edward P. Riley Background: Prenatal alcohol exposure can lead to widespread cognitive impairment and behav- ioral dysregulation, including deficits in attention and response inhibition. This study characterized the neural substrates underlying the disinhibited behavioral profile of individuals with fetal alcohol spectrum disorders (FASD). Methods: Children and adolescents (ages 8–18) with (n 5 13) and without (n 5 9) histories of heavy prenatal alcohol exposure underwent functional magnetic resonance imaging while performing a response inhibition (go/no-go) task. Results: Despite similar task performance (mean response latency, performance accuracy, and signal detection), blood oxygen level-dependent (BOLD) response patterns differed by group. Region-of-interest analyses revealed that during portions of the behavioral task that required response inhibition, alcohol-exposed participants showed greater BOLD response across prefrontal cortical regions (including the left medial and right middle frontal gyri), while they showed less right caudate nucleus activation, compared with control participants. Conclusions: These data provide an account of response inhibition-related brain functioning in youth with FASD. Furthermore, results suggest that the frontal–striatal circuitry thought to mediate inhibitory control is sensitive to alcohol teratogenesis. Key Words: Fetal Alcohol Spectrum Disorders, Response Inhibition, Functional Neuroimaging, Fetal Alcohol Syndrome. A LTHOUGH FETAL ALCOHOL syndrome (FAS) has been clinically recognized for decades, it is now acknowledged that prenatal alcohol exposure can be asso- ciated with cognitive and behavioral deficits, even in the absence of the facial features and physical growth retarda- tion required to make a diagnosis of FAS. Accordingly, fetal alcohol spectrum disorders (FASD) is used as an umbrella term to describe the range of effects attributable to gestational alcohol exposure. The incidence of FASD has been conservatively estimated at 9 per 1,000 live births (Sampson et al., 1997). Individuals with histories of heavy prenatal alcohol exposure may present with a range of cognitive dysfunctions, including deficits in general intelligence, attention, learning, memory, visuo-spatial cognition, and psychomotor skills (Autti-Ra¨mo¨, 2000; Mattson and Riley, 1998; Streissguth et al., 2004). Executive functioning (EF) is a heterogeneous neuropsy- chological concept encompassing integrative higher-order cognitive abilities that include behavioral inhibition, work- ing memory, planning, and set shifting (Pennington and Ozonoff, 1996). Anecdotally, individuals with histories of prenatal alcohol exposure are described as lacking in EF-based skills. For example, they may exhibit poor judg- ment, show impairments in planning and problem solving, or fail to anticipate the consequences of their actions. Neu- ropsychological assessment has demonstrated deficits in individuals with prenatal alcohol exposure histories across various EF abilities including cognitive planning and flex- ibility (Kodituwakku et al., 1995; Mattson et al., 1999), and it has been suggested that at least some of the EF deficits associated with prenatal alcohol exposure occur above and beyond general intellectual deficits (Connor et al., 2000). A task that taps response inhibition was chosen for the present study, because the disinhibited, disruptive behavioral profile reported in individuals with FASD con- tributes to dysfunction in school, employment, and social settings. Impairment in response inhibition, an aspect of EF, has been proposed as a potential mechanism underly- ing disruptive behavior disorders (Nigg, 2003; Sergeant et al., 2002). This theoretical framework may be useful in considering the effects of prenatal alcohol exposure, as inattention and misconduct are frequently observed in From the Joint Doctoral Program in Clinical Psychology, San Diego State University/University of California, San Diego, California (SLF, ADS); the Department of Psychiatry, University of California, San Diego, California (SFT, MPP); the VA San Diego Healthcare System, San Diego, California (SFT, MPP); and the Department of Psychology and the Center for Behavioral Teratology, San Diego State University, San Diego, California (SNM, EPR). Received for publication October 3, 2006; accepted March 30, 2007. Research supported by NIAAA: R01 AA10417, T32 AA013525 to EPR, R01 AA10820 and U01 AA14834 to SNM, and F31 AA016051 to SLF. Reprint requests: S. L. Fryer, MS, 6363 Alvarado Court, Suite 200 San Diego, CA 92120; Fax: 619-594-1895; E-mail: sfryer@ucsd.edu Copyright r 2007 by the Research Society on Alcoholism. DOI: 10.1111/j.1530-0277.2007.00443.x Alcohol Clin Exp Res, Vol 31, No 8, 2007: pp 1 – 10 1 ALCOHOLISM:CLINICAL AND EXPERIMENTAL RESEARCH Vol. 31, No. 8 August 2007